Brief Report: Delayed Diagnosis of Treatable Inborn Errors of Metabolism in Children with Autism and Other Neurodevelopmental Disorders

Márquez-Caraveo, María Elena; Ibarra-González, Isabel; Rodríguez-Valentín, Rocío; Ramírez-García, Miguel Ángel; Pérez-Barrón, Verónica; Lazcano‐Ponce, Eduardo; Vela-Amieva, Marcela

doi:10.1007/s10803-020-04682-2

Cited by 8 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study group, we also found that 7/10 older siblings had a diagnostic odyssey, and they were frequently misdiagnosed with unspecified motor and intellectual disability (Table 3). This situation is common in low-income countries and has been described for several IEMs [35][36][37]. Thus, training physicians in IEMs and in neurodevelopmental skills is imperative in order to favor early detection of patients and to prevent or ameliorate health damage.…”

Section: Discussionmentioning

confidence: 99%

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Ibarra-González

Fernández-Lainez

Guillén-López

et al. 2021

J. inborn errors metab. screen.

Self Cite

View full text Add to dashboard Cite

Introduction: Any abnormal newborn screening (NBS) test should be subjected to appropriate diagnostic tests and should be followed. Once the newborn has been diagnosed and treated, the family should receive comprehensive genetic services. Aim: To present the experience of studying older siblings of patients with inborn errors of metabolism (IEM) identified by NBS in a single-national follow-up reference center. Methods: A retrospective analysis of medical files of the IEM patients detected by NBS was conducted. All those older siblings who tested positive for the same IEM of the patient detected by newborn screening were included. Results: A total of 26 positive siblings from 18 families with seven different IEM were found (phenylketonuria, argininemia, glucose-6-phosphate dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, dihydropteridine reductase deficiency, tyrosinemia type 3, and medium chain acyl-CoA dehydrogenase deficiency). The age range of the affected siblings was 2 to 19 years old, with a mean age of 8.5 years. Ten older siblings (38.5%) had clinical consequences for the disease, including severe intellectual disability. Conclusions: It is necessary to study older siblings, and family history and genetic counseling of all NBS-detected families should be recommended, especially in countries where expanded NBS programs are beginning.

show abstract

Section: Discussionmentioning

confidence: 99%

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Ibarra-González

Fernández-Lainez

Guillén-López

et al. 2021

J. inborn errors metab. screen.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, with the NBS programs, especially in developed countries, many such individuals are brought to medical attention early, and necessary treatments are instigated; a good example is phenylalanine ketonuria, an IMD characterized by intellectual disability and ASD [ 52 , 63 , 98 ]. Therefore, the diagnostic approach to ASD should be equipped with a rational consideration of possible IMDs, as some are treatable [ 54 ]. A recently suggested approach to such investigation is untargeted metabolomic profiling, as many ASD patients demonstrate a wide range of metabolic abnormalities, from micronutrient deficiencies to severe metabolic derangements [ 99 ].…”

Section: Biochemical Investigationsmentioning

confidence: 99%

Biochemical, Genetic and Clinical Diagnostic Approaches to Autism-Associated Inherited Metabolic Disorders

Senarathne

Indika

Jezela‐Stanek³

et al. 2023

Genes

View full text Add to dashboard Cite

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by impaired social interaction, limited communication skills, and restrictive and repetitive behaviours. The pathophysiology of ASD is multifactorial and includes genetic, epigenetic, and environmental factors, whereas a causal relationship has been described between ASD and inherited metabolic disorders (IMDs). This review describes biochemical, genetic, and clinical approaches to investigating IMDs associated with ASD. The biochemical work-up includes body fluid analysis to confirm general metabolic and/or lysosomal storage diseases, while the advances and applications of genomic testing technology would assist with identifying molecular defects. An IMD is considered likely underlying pathophysiology in ASD patients with suggestive clinical symptoms and multiorgan involvement, of which early recognition and treatment increase their likelihood of achieving optimal care and a better quality of life.

show abstract

“…While metabolic abnormalities have been found in patients with such NDDs as ASD (an increase in lactate and creatine and a decrease in creatinine are among many suggested changes that have been reported [ 127 , 139 , 142 , 143 , 144 ]), Rett syndrome (MIM# 312750; metabolites associated with urea and the Krebs cycle and the metabolism of certain amino acids [ 145 ]) and Down syndrome (MIM# 190685; alterations to methylation metabolism, carnitine/O-acetylcarnitine, dimethyl sulfone, and myo-inositol [ 143 ]), the group of disorders where metabolomics has the most obvious diagnostic application is that of inborn errors of metabolism (IEM), affecting 1:1000 to 1:2000 newborns [ 137 , 146 ]. To date, there are 1615 known IEM and over a half of them show neurologic involvement, including at least 231 presenting with a movement disorder and at least 116 treatable IEMs causing intellectual disability [ 147 , 148 , 149 , 150 , 151 ]. It has also been suggested that ASD patients, at least those born outside of high income countries, are underdiagnosed for IEM [ 148 ].…”

Section: Integrating Omics To Understand Functional Effects and Impro...mentioning

confidence: 99%

“…To date, there are 1615 known IEM and over a half of them show neurologic involvement, including at least 231 presenting with a movement disorder and at least 116 treatable IEMs causing intellectual disability [ 147 , 148 , 149 , 150 , 151 ]. It has also been suggested that ASD patients, at least those born outside of high income countries, are underdiagnosed for IEM [ 148 ]. An online tool, Treatable ID App, has been created to assist clinicians in selecting a targeted metabolic workup.…”

Section: Integrating Omics To Understand Functional Effects and Impro...mentioning

confidence: 99%

Methods to Improve Molecular Diagnosis in Genomic Cold Cases in Pediatric Neurology

Kadlubowska

Schrauwen

2022

Genes

View full text Add to dashboard Cite

During the last decade, genetic testing has emerged as an important etiological diagnostic tool for Mendelian diseases, including pediatric neurological conditions. A genetic diagnosis has a considerable impact on disease management and treatment; however, many cases remain undiagnosed after applying standard diagnostic sequencing techniques. This review discusses various methods to improve the molecular diagnostic rates in these genomic cold cases. We discuss extended analysis methods to consider, non-Mendelian inheritance models, mosaicism, dual/multiple diagnoses, periodic re-analysis, artificial intelligence tools, and deep phenotyping, in addition to integrating various omics methods to improve variant prioritization. Last, novel genomic technologies, including long-read sequencing, artificial long-read sequencing, and optical genome mapping are discussed. In conclusion, a more comprehensive molecular analysis and a timely re-analysis of unsolved cases are imperative to improve diagnostic rates. In addition, our current understanding of the human genome is still limited due to restrictions in technologies. Novel technologies are now available that improve upon some of these limitations and can capture all human genomic variation more accurately. Last, we recommend a more routine implementation of high molecular weight DNA extraction methods that is coherent with the ability to use and/or optimally benefit from these novel genomic methods.

show abstract

Brief Report: Delayed Diagnosis of Treatable Inborn Errors of Metabolism in Children with Autism and Other Neurodevelopmental Disorders

Cited by 8 publications

References 26 publications

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Biochemical, Genetic and Clinical Diagnostic Approaches to Autism-Associated Inherited Metabolic Disorders

Methods to Improve Molecular Diagnosis in Genomic Cold Cases in Pediatric Neurology

Contact Info

Product

Resources

About